title: LFA-1-mediated adhesion is regulated by cytoskeletal restraint and by a Ca2+-dependent protease, calpain.
abstract: The activity of integrins on leukocytes is kept under tight control to avoid inappropriate adhesion while these cells are circulating in blood or migrating through tissues. Using lymphocyte function-associated antigen-1 (LFA-1) on T cells as a model, we have investigated adhesion to ligand intercellular adhesion molecule-1 induced by the Ca2+ mobilizers, ionomycin, 2, 5-di-t-butylhydroquinone, and thapsigargin, and the well studied stimulators such as phorbol ester and cross-linking of the antigen-specific T cell receptor (TCR)-CD3 complex. We report here that after exposure of T cells to these agonists, integrin is released from cytoskeletal control by the Ca2+-induced activation of a calpain-like enzyme, and adhesive contact between cells is strengthened by means of the clustering of mobilized LFA-1 on the membrane. We propose that methods of leukocyte stimulation that cause Ca2+ fluxes induce LFA-1 adhesion by regulation of calpain activity. These findings suggest a mechanism whereby engagement of the TCR could promote adhesion strengthening at an early stage of interaction with an antigen-presenting cell.
authors.affiliation: Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.
authors.forename: M P
authors.initials: MP
authors.lastname: Stewart
authors.forename: A
authors.initials: A
authors.lastname: McDowall
authors.forename: N
authors.initials: N
authors.lastname: Hogg
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism*; D002448:Cell Adhesion; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000502:physiology; D047630:Depsipeptides; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis / Q000502:physiology*; D018613:Microscopy, Confocal; D010456:Peptides, Cyclic / Q000494:pharmacology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D047630:Depsipeptides; D006873:Hydroquinones; D016169:Lymphocyte Function-Associated Antigen-1; D010456:Peptides, Cyclic; C057531:jasplakinolide; D018799:Intercellular Adhesion Molecule-1; C019359:2,5-di-tert-butylhydroquinone; D015759:Ionomycin; D019284:Thapsigargin; D002154:Calpain; D002118:Calcium